Elsevier

Experimental Gerontology

Volume 48, Issue 11, November 2013, Pages 1226-1235
Experimental Gerontology

Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys

https://doi.org/10.1016/j.exger.2013.08.002Get rights and content

Highlights

  • We examined the very long-term effect of calorie restriction (CR) in rhesus monkeys.

  • CR was found to reduce sleeping metabolic rate and the energy cost of movement.

  • Physical activity as measured by movement decreases during aging in control group.

  • However, CR prevents the age-associated decrease in the physical activity.

  • These differences are the opposite of those usually observed during short-term CR.

Abstract

Background

Short-term (< 1 year) calorie restriction (CR) has been reported to decrease physical activity and metabolic rate in humans and non-human primate models; however, studies examining the very long-term (> 10 year) effect of CR on these parameters are lacking.

Objective

The objective of this study was to examine metabolic and behavioral adaptations to long-term CR longitudinally in rhesus macaques.

Design

Eighteen (10 male, 8 female) control (C) and 24 (14 male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old were examined after 13 and 18 years of moderate adult-onset CR. Energy expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory chamber (24 h EE). Physical activity was assessed both by metabolic equivalent (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of movements during 24 h was also calculated. Age and fat-free mass were included as covariates.

Results

Adjusted total and 24 h EE were not different between C and CR. Sleeping metabolic rate was significantly lower, and physical activity level was higher in CR than in C independent from the CR-induced changes in body composition. The duration of physical activity above 1.6 METs was significantly higher in CR than in C, and CR had significantly higher accelerometer activity counts than C. Metabolic cost of movements during 24 h was significantly lower in CR than in C. The accelerometer activity counts were significantly decreased after seven years in C animals, but not in CR animals.

Conclusions

The results suggest that long-term CR decreases basal metabolic rate, but maintains higher physical activity with lower metabolic cost of movements compared with C.

Introduction

The concept of delaying the morbidities of aging through caloric restriction (CR) can be traced back at least three centuries to, Kaibara Ekiken (1630–1714) who wrote at the age of 83 years in his Yōjōkun (The Book of Life-nourishing Principles) that one way to remain healthy and increase longevity is to stop eating when the stomach is less than full (Kaibara and Translated by Wilson, 2009 (originally written in 1712)). Far more recently, careful laboratory studies of CR without malnutrition have shown that CR does indeed extend the maximal life span in multiple short-lived species (Anderson et al., 2009). In nonhuman primates, CR has been shown to reduce or delay the onset of diverse age-related diseases and disorders such as diabetes (Gresl et al., 2001), sarcopenia (Colman et al., 2008), immune senescence (Messaoudi et al., 2006), hypertension, cancer, bone demineralization, and brain atrophy (Colman and Anderson, 2011, Colman et al., 2009). The study of rhesus monkeys at the University of Wisconsin, begun in 1989, also demonstrated a reduction in age-related mortality in CR animals (Colman and Anderson, 2011, Colman et al., 2009), although an effect on longevity was not found in a second study performed at the National Institute of Aging (Mattison et al., 2012).

In rhesus monkeys CR is associated with an initial weight loss, but body weight plateaus indicating that caloric balance is reestablished during the CR intervention (Colman et al., 2008). The metabolic transition is characterized by a decrease in energy expenditure (Ramsey et al., 2000a), presumably to match the reduction in energy intake. Randomized controlled trials for CR have shown that much of the adaptation is driven by a reduction in body size, but reductions in energy expenditure that cannot be explained simply by the smaller body size have been reported (DeLany et al., 1999, Ramsey et al., 1997, Weed et al., 1997), although findings are inconsistent (Kemnitz et al., 1993, Moscrip et al., 2000, Ramsey et al., 1997, Weed et al., 1997).

Daily energy expenditure has three major components: resting metabolic rate, the thermic effect of food, and the energy expenditure of physical activity. Most studies to date have focused on resting metabolic rate and total energy expenditure. Physical activity has also been studied and earlier reviews of the subject concluded that CR did not alter physical activity in macaques (Heilbronn and Ravussin, 2003, Ingram et al., 2001, Roth et al., 2002). In rodent studies, however, differing results have been reported; specifically, it has been found that wheel-running activity of rats was generally reduced in CR groups early in life, but CR resulted in higher activity levels later in life when control groups began to exhibit a marked age related decline in activity (Goodrick et al., 1983).

The objective of this current study was to determine the metabolic and behavioral adaptations to long-term diet restriction in rhesus monkeys. Longitudinal changes in energy expenditure including the metabolic cost of movement, and duration and intensity of physical activity during 24 h were determined in monkeys enrolled in the on-going University of Wisconsin CR and Aging study (Kemnitz et al., 1993, Ramsey et al., 2000a). The youngest animals in this longitudinal study were 19 years of age at the last assessment time-point for this analysis, an age considered past the age of sarcopenia onset, which has been clinically assessed to be 14–16 years of age in rhesus monkeys at the Wisconsin National Primate Research Center (WNPRC) (Colman et al., 2005).

Section snippets

Animals

The CR study at WNPRC has been previously described (Kemnitz et al., 1993, Ramsey et al., 1997). Briefly, the study includes three groups of adult rhesus monkeys (Macaca mulatta of Indian derivation); 30 male monkeys entered in the study in 1989 (Group 1), and 30 females (Group 2) and an additional 16 males (Group 3) were introduced in 1994. All groups averaged ~ 10 years of age at the onset of CR. Within each group animals were stratified by body weight and randomly assigned to either the

Dietary intake

The impact of age on calorie intake has influenced the extent of CR achieved in this study over time. Until 2001 the difference in energy intake between C and CR had been about 28–30% (Blanc et al., 2003); however, the difference in energy intake between C and CR decreased thereafter. As the study progressed, the 18 C animals ate 11% less than at the outset of the study (2.72 MJ/d at 1999 to 2.41 MJ/d at 2007, P = 0.020 by paired t-test). Energy intake did not change over the same period for the 24

Discussion

The present study provides the most comprehensive analysis of energy expenditure in nonhuman primates under control and CR conditions conducted to date. To circumvent the prior limitation of possible night-time wakefulness, we refined our proxy resting metabolic rate measurement by using a sleeping metabolic rate (lowest 3 h night time energy expenditure) in place of a 12 h night-time metabolic rate, and confirmed our previous report of reduced resting metabolic rate among CR animals (Blanc et

Conclusion

Short-term (< 1 yr) calorie restriction (CR) lowers TEE, activity energy expenditure, and physical activity in human and non-human primates. In long-term CR, however, CR does not decrease either TEEDLW or 24 h EEchamber even though SMR is lower in CR non-human primates. Furthermore, CR animals maintain a higher physical activity level than C animals, with significantly longer duration of physical activity and more frequent high intensity activities observed in CR animals. Importantly, the metabolic

Conflict of interest

The authors have no conflicts of interests.

Acknowledgment

This work was supported by grants P01 AG-11915 (to R. Weindruch) and P51 RR000167 (to the Wisconsin National Primate Research Center, University of Wisconsin, Madison). This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01.

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